The overall objective of this proposal is to elucidate the molecular basis of mitogenic activation of lymphocytes from healthy individuals and patients with chronic lymphocytic leukemia. We propose to examine cell-cell interactions and biochemical events that occur during activation of lymphocytes with sodium periodate (NaIO4) and galactose oxidase. First we will examine the role played by different cells (stimulator cells, responder cells, and adherent cells) in oxidative activation of lymphocyte cultures. Cells will be physically separated by means of agarose to examine the participation of soluble factors in the early stages of activation. Attempts to detect unique surface components will be made by application of lectin-Sepharose columns and two-dimensional gel electrophoresis. A soluble factor from adherent cells and a lymphocyte growth factor elicited during oxidative activation will be characterized by application of these methods. After defining the requirements for and the soluble components involved in the activation of normal lymphocytes, we plan to compare biochemical differences between lymphocytes obtained from healthy donors and those from patients with chronic lymphocytic leukemia.